Nucleotide Regulation of Soluble Guanylate Cyclase Substrate Specificity

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• 作者：Emily R. Derbyshire ; Nathaniel B. Fernhoff ; Sarah Deng ; Michael A. Marletta
• 刊名：Biochemistry
• 出版年：2009
• 出版时间：August 11, 2009
• 年：2009
• 卷：48
• 期：31
• 页码：7519-7524
• 全文大小：773K
• 年卷期：v.48,no.31(August 11, 2009)
• ISSN：1520-4995

文摘

Soluble guanylate cyclase (sGC) serves as a receptor for the signaling agent nitric oxide (NO). sGC synthesis of cGMP is regulated by NO, GTP, ATP, and allosteric activators such as YC-1. The guanylate cyclase activity and adenylate cyclase activity of full-length sGC and the sGC catalytic domain constructs (α1_catβ1_cat) are reported here. ATP is a mixed-type inhibitor of cGMP production for both sGC and α1_catβ1_cat, indicating that the C-terminus of sGC contains an allosteric nucleotide binding site. YC-1 did not activate α1_catβ1_cat or compete with ATP inhibition of cGMP synthesis, which suggests that YC-1 and ATP bind to distinct sites. α1_catβ1_cat and NO-stimulated sGC also synthesize cAMP, but this activity is inhibited by ATP via noncompetitive substrate inhibition and by GTP via mixed-type inhibition. Additionally, the adenylate cyclase activity of purified sGC was inhibited by PC12 lysate, suggesting that an intracellular small molecule or protein regulates this activity in vivo.